Abstract:
:For FDA approval, bioequivalence of a generic version of Tacrolimus must be demonstrated in a randomized, two-treatments, two-periods, two-sequences, single-dose crossover study in healthy adult volunteers. Currently there are at least 3 differents generic equivalent for Tacrolimus, that are approved by the EMA and the FDA, with a USA market share of nearly 50%. However, the market share of generic immunosuppressive drugs in the Middle East region is still very low due to the reluctance of the physician to accept Tacrolimus generics, considered to be a narrow therapeutic window drug, that are approved using the standard bioequivalence criteria of 80% to 125%. Herein we present a bioequivalence study of a new Tacrolimus generic, Tacrolimus Medis 5 mg developed by Medis Tunisia batch number 12G3003 compared with Prograf® 5 mg batch number 7202 manufactured by Astellas Toyama Co., Ltd. Japan and HIKMA Pharmaceuticals, Amman-Jordan in healthy adult volunteers using the 90%-111% criteria recommended for drugs with narrow therapeutic window. The study was, balanced, randomized, two-treatments, two-periods, two-sequences, single dose, crossover, comparative oral bioavailability study in healthy adult human volunteers. The study was carried out in accordance with the Basic Principles defined in the U.S. 21 CFR Part 312.20, the principles enunciated in the Declaration of Helsinki (World Medical Association Declaration of Helsinki). Thirty six non-smoking healthy, as determined by medical history, volunteers, 18 years and older, were included. Following randomization using a computer software (pharma solution) the volunteers were given a single oral dose of 5 milligrams following a 12 hour fast with a wash out period of 7 days. Pharmacokinetics profile with blood levels at: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, and 24 hours were performed following each dose. Tacrolimus plasma level was determined using an HPLC validated method (Transmedical For Life S.A.R.L. Beirut Lebanon), for accuracy, suitability, reproducibility, precision , long-term stability and robustness. Physical examinations, hematology, urine analysis and serum chemistry tests were performed at screening and before dosing in each period and at end of the study. Volunteers were monitored for safety and adverse events throughout the study. Both products were bioequivalent at the entire pharmacokinetic parameters tested. The LSM were 95.31%-101.21% for AUC, 94.65%-101.11% for AUC0-inf, 97.15%-100.02% for Cmax and 91.54%-103.75% for Half-life. Respectively all of which are within the EU and FDA approval limits (90-111%) indicating that the 2 products are equivalent and switchable.
journal_name
Transplant Procjournal_title
Transplantation proceedingsauthors
Masri M,Rizk S,Boujbel L,Bellahirich W,Baassoumi D,Attia M,Matha Vdoi
10.1016/j.transproceed.2013.08.104subject
Has Abstractpub_date
2013-01-01 00:00:00pages
3453-7issue
10eissn
0041-1345issn
1873-2623pii
S0041-1345(13)00909-3journal_volume
45pub_type
杂志文章,随机对照试验abstract:OBJECTIVE:The aim of this study was to evaluate the effects of using thromboembolic deterrent (TED) stockings and intermittent pneumatic compression (IPC) vs a muscle pump activator (MPA) device on limb edema and patient satisfaction after transplant. METHODS:In this single-center randomized controlled trial, 118 pati...
journal_title:Transplantation proceedings
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.transproceed.2019.04.032
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Screening for neoplastic lesions is mandatory as a part of the evaluation process of potential candidates for liver transplant (LT). This work aimed at identifying the main findings in screening colonoscopy and their risk factors. METHODS:Endoscopic and pathologic findings of the biopsied lesions of 311 pot...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2019.10.026
更新日期:2020-01-01 00:00:00
abstract::Donor cause of death (DCOD) has been described to influence allograft survival. Whether this effect is independent of other donor characteristics and whether it is similar across different solid organ allografts is not known. The aim of our study was to determine the impact of DCOD on organ utilization and on transpla...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2009.06.192
更新日期:2009-11-01 00:00:00
abstract:BACKGROUND:Cold ischemia and clamping of the renal artery contribute to acute tubular necrosis and renal dysfunction of transplant grafts. The mechanism of ischemic injury is not fully understood, but endothelin (ET)-1 and -2 have been found to participate in reperfusion injury. ET receptor blockade has been shown to h...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2008.02.071
更新日期:2008-06-01 00:00:00
abstract::In September 2001, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) founded the Collaborative Islet Transplant Registry (CITR). Each year, CITR produces a complete set of analyses available to the public. In its second year, CITR represents the efforts of 19 North American islet transplant ...
journal_title:Transplantation proceedings
pub_type: 杂志文章,多中心研究
doi:10.1016/j.transproceed.2006.10.014
更新日期:2007-01-01 00:00:00
abstract:UNLABELLED:Certain characteristics of the donor have implications for the early and late survival of transplants. The trends show a progressive worsening in the clinical profile of heart donors. Our objective was to analyze changes in the clinical characteristics of donors. MATERIALS AND METHODS:This retrospective stu...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2006.08.021
更新日期:2006-10-01 00:00:00
abstract:INTRODUCTION:Liver transplant is the only option in reversing liver insufficiency and its complications. It is very important to realize the quality control of organs and tissues used in transplant, as well as to develop diagnostic, treatment, and prophylaxis techniques to prevent other comorbidities and to increase th...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2020.01.073
更新日期:2020-06-01 00:00:00
abstract::An isolated perfused rat liver model was used to investigate biochemical and histologic changes during 2 hours of reperfusion after 24 hours of cold storage to compare Leeds solution (LS) with University of Wisconsin solution (UW). Compared with livers stored in UW, those perfused with LS showed significantly higher b...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2010.06.029
更新日期:2010-11-01 00:00:00
abstract:BACKGROUND:Granulocyte and monocyte adsorptive apheresis (GMAA) is widely used as a treatment for active ulcerative colitis (UC) in Japan. Much attention has been paid to the possibility of GMAA for the treatment and control of cytomegalovirus (CMV) reactivation in patients with refractory UC and concomitant CMV infect...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2015.12.127
更新日期:2016-04-01 00:00:00
abstract::There was no statistical significance to the differences in waiting time for cadaveric renal transplant by race. Whether for first transplant or second or greater, any differences in waiting time could not be accounted for by the recipient's race. CAUC made up 58% of the waiting list, 65% of the recipients, and 87% of...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:
更新日期:1991-10-01 00:00:00
abstract::In renal ischemia/reperfusion (I/R) injury endothelial cells are a main target. The disturbance of endothelial cell physiology leads to endothelial swelling and narrowing of the blood vessel lumen. We attribute this effect to impairment of endothelial cell nitric oxide synthase (NOS). NO is significantly reduced in th...
journal_title:Transplantation proceedings
pub_type: 杂志文章,评审
doi:10.1016/j.transproceed.2006.01.059
更新日期:2006-04-01 00:00:00
abstract:OBJECTIVE:Our goal was to analyze the morbidity of organic erectile dysfunction (ED) in kidney-transplant patients and to evaluate the efficacy and reliability of sildenafil citrate treatment. METHOD:Sixty-five ED patients with normal graft function for 3 to 12 months after kidney transplantation were involved in our ...
journal_title:Transplantation proceedings
pub_type: 临床试验,杂志文章
doi:10.1016/j.transproceed.2005.03.026
更新日期:2005-06-01 00:00:00
abstract::Recent therapeutic strategies to combat organ allograft rejection have focused on T-cell signaling pathways and the molecules that comprise them. The macrolide antibiotic produced by the bacterium Streptomyces hygroscopicus, known as sirolimus or rapamycin, has shown great therapeutic potential in the transplant setti...
journal_title:Transplantation proceedings
pub_type: 杂志文章,评审
doi:10.1016/s0041-1345(03)00230-6
更新日期:2003-05-01 00:00:00
abstract:BACKGROUND:Nowadays pregnancy after organ transplantation is possible due to advances in surgical and immunosuppressive therapies. One of the possible complications in pregnancy after organ transplantation is intrauterine growth restriction (IUGR). This may lead to various adverse perinatal outcomes. Prevalence of IUGR...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2014.09.001
更新日期:2014-10-01 00:00:00
abstract::We investigated whether blockade of nitric oxide synthase by the arginine analog l- NAME could affect peripheral liver blood flow (PLBF) or hepatocyte integrity (serum ALT) in either a control series or in a series subjected to mild reduction of liver blood flow by temporary clamping of the hepatic artery (HA). Anesth...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2005.09.135
更新日期:2005-10-01 00:00:00
abstract::The demand for organ transplantation has rapidly increased all over the world during the past decade due to the increased incidence of vital organ failure, the rising success and greater improvement in posttransplant outcome. However, the unavailability of adequate organs for transplantation to meet the existing deman...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2007.11.067
更新日期:2008-01-01 00:00:00
abstract::Clinical cell transplantation remains as a clinical experiment. Morphologically intact and functional cells transplanted into their tissue of origin undergo rapid disintegration by attacking granulocytes and macrophages, leading to the so-called early graft dysfunction. When transplanted to sites remote from their ori...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/s0041-1345(03)00779-6
更新日期:2003-09-01 00:00:00
abstract::We performed 24-hour monitoring of cyclosporine (NEO) and tacrolimus (TAC) blood concentrations, evaluating pharmacokinetic parameters and characterizing circadian variations. The monitoring was performed in 10 instances on nine patients administered NEO and 12 out of 11 patients administered TAC. All cases were admin...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2005.02.104
更新日期:2005-05-01 00:00:00
abstract::Perineuriomas are rare, benign peripheral nerve sheath tumors, most commonly found in the extremities and trunks. A handful of cases have been reported to arise from the retroperitoneum and in kidneys. To our knowledge, this is the first reported case of a myxoid perineurioma arising from a transplanted kidney. The pa...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2013.09.030
更新日期:2014-01-01 00:00:00
abstract::Cytomegalovirus (CMV) seronegative renal allograft recipients (R-), particularly those with a graft from a CMV-seropositive donor (D+), are at high risk for primary CMV infection. CMV resistance to antiviral oral therapy is an emerging problem in renal transplantation, prompting development of new prophylactic strateg...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2006.07.001
更新日期:2006-09-01 00:00:00
abstract:PURPOSE:The family advocate plays a crucial role in the organ and tissue procurement process for transplantation and research. This responsibility can weigh profoundly on the consent/conversion rates for family advocates. Some potential donor families consider time as a critical factor when deciding to donate. It was h...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2008.03.058
更新日期:2008-05-01 00:00:00
abstract::The metabolic syndrome (MetS) is a risk factor for posttransplant diabetes mellitus, chronic graft dysfunction, graft loss, occurrence of atherosclerotic events, and patient death among kidney transplantation patients. Long-acting natriuretic peptide (LANP) is among the peptide hormones in atrial natriuretic peptide p...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2011.11.008
更新日期:2012-04-01 00:00:00
abstract:INTRODUCTION:Pneumonia remains a significant cause of morbidity and mortality after kidney transplantation. The present study was therefore conducted to investigate whether or not the polymorphisms of tumor necrosis factor (TNF)β, interleukin (IL)-10, IL-1β, and IL-1 receptor antagonist (IL-1ra) gene predicted the susc...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2013.02.122
更新日期:2013-07-01 00:00:00
abstract:OBJECTIVES:The clinical and biochemical manifestations of acute rejection after liver transplantation are nonspecific, and a liver biopsy is often needed to verify the diagnosis. This may delay treatment. The aim of this study was to evaluate whether monitoring of intrahepatic glucose, lactate, pyruvate, and glycerol b...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2020.02.157
更新日期:2021-01-01 00:00:00
abstract:INTRODUCTION:Diagnosis of thyroid disease is fundamental in the evaluation of patients awaiting kidney transplantation. We analyzed the incidence of thyroid disease in patients with end-stage renal disease (ESRD) and evaluated its evolution before and after kidney transplantation. PATIENTS AND METHODS:Between January ...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2009.03.014
更新日期:2009-05-01 00:00:00
abstract::Hypertension is one of the most frequent complications of renal transplantation. About 70% to 90% of this population display either high blood pressure (BP) or require antihypertensive therapy. Diabetes mellitus is also a common finding among kidney transplant recipients. The aim of the study was to assess the BP cont...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2012.05.089
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Preoperative cardiac troponin-I (cTnI) elevation has been shown to be a predictor of mortality after liver transplantation. Myocardial injury after non-cardiac surgery (MINS) has been defined as elevation of serum cardiac troponin levels in the perioperative period that does not fulfill the criteria for myoc...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2019.02.046
更新日期:2019-09-01 00:00:00
abstract:INTRODUCTION:Our aim was to evaluate the influence on yield and function of intrathoracic organs from donors after severe cranial trauma complicated by disseminated intravascular coagulation (DIC). MATERIALS AND METHODS:This retrospective observational study in a patient cohort with severe cranial trauma reading to br...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2007.07.052
更新日期:2007-09-01 00:00:00
abstract::Treatment with cyclosporine (CsA) markedly affects the renin-angiotensin-aldosterone system in parallel with an increase in the net tubular reabsorption or a decrease in secretion. Since tubular reabsorption is closely linked to medullary oxygen consumption, the aim of the present study was to investigate the intraren...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2005.09.013
更新日期:2005-10-01 00:00:00
abstract:BACKGROUND:Animal models of partial hepatic ischemia-reperfusion injury (IRI) have potential benefits for decision making and clinical management after liver transplantation or massive hepatic resection. We evaluated changes in apparent diffusion coefficient (ADC) in rabbits with partial hepatic IRI using 3.0 T magneti...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2011.01.183
更新日期:2011-06-01 00:00:00